NCT03696108

A Study of Gefapixant (MK-7264) in Japanese Adult Participants With Refractory or Unexplained Chronic Cough (MK-7264-038)

Completed Phase 3 Results posted Last updated 1 November 2021

What this trial tests

Phase 3 trial testing Gefapixant in Chronic Cough in 175 participants. Completed in 7 October 2020.

Timeline

31 October 2018

Primary endpoint
7 October 2020

7 October 2020

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	175
Start date	31 October 2018
Primary completion	7 October 2020
Estimated completion	7 October 2020
Sites	61 locations across Japan

Drugs / interventions tested

• Gefapixant — full drug profile →
• Placebo

Conditions studied

• Chronic Cough — all drugs for Chronic Cough →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

20 and older, any sex, with Chronic Cough. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced at Least One Adverse Event (AE) Primary · Up to 54 Weeks

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Group	Value	95% CI
Gefapixant 15 mg BID	79
Gefapixant 45 mg	82

Number of Participants Who Discontinued Study Drug Due to an AE Primary · Up to 52 Weeks

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Group	Value	95% CI
Gefapixant 15 mg BID	6
Gefapixant 45 mg	17

Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 Secondary · Baseline, Week 12

The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model.

Group	Value	95% CI
Gefapixant 15 mg BID	1.4	0.7 – 2.0
Gefapixant 45 mg	0.9	0.3 – 1.6

Change From Baseline in LCQ Total Score Secondary · Baseline, up to 52 Weeks

The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model at weeks 4, 8, 12, 24, 38 and 52 of treatment.

Week 4

Group	Value	95% CI
Gefapixant 15 mg BID	0.9	0.2 – 1.5
Gefapixant 45 mg	0.8	0.2 – 1.4

Week 8

Group	Value	95% CI
Gefapixant 15 mg BID	1.5	0.8 – 2.1
Gefapixant 45 mg	1.2	0.6 – 1.9

Week 12

Group	Value	95% CI
Gefapixant 15 mg BID	1.4	0.7 – 2.0
Gefapixant 45 mg	0.9	0.3 – 1.6

Week 24

Group	Value	95% CI
Gefapixant 15 mg BID	1.6	0.9 – 2.2
Gefapixant 45 mg	1.1	0.4 – 1.8

Week 38

Group	Value	95% CI
Gefapixant 15 mg BID	1.8	1.1 – 2.4
Gefapixant 45 mg	1.2	0.6 – 1.9

Week 52

Group	Value	95% CI
Gefapixant 15 mg BID	2.3	1.6 – 2.9
Gefapixant 45 mg	1.5	0.8 – 2.1

Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score Secondary · Baseline, Up to 52 Weeks

The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at weeks 4, 8, 12, 24, 38 and 52 of treatment.

Week 4

Group	Value	95% CI
Gefapixant 15 mg BID	38.1
Gefapixant 45 mg	36.5

Week 8

Group	Value	95% CI
Gefapixant 15 mg BID	43.4
Gefapixant 45 mg	43.2

Week 12

Group	Value	95% CI
Gefapixant 15 mg BID	48.2
Gefapixant 45 mg	40.7

Week 24

Group	Value	95% CI
Gefapixant 15 mg BID	53.7
Gefapixant 45 mg	45.7

Week 38

Group	Value	95% CI
Gefapixant 15 mg BID	56.1
Gefapixant 45 mg	44.9

Week 52

Group	Value	95% CI
Gefapixant 15 mg BID	58.8
Gefapixant 45 mg	46.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 54 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Gefapixant 15 mg

Serious: 2/84 (2%)

Deaths: 0/84

Gefapixant 45 mg

Serious: 10/85 (12%)

Deaths: 0/85

Serious adverse events (11 terms)

Reaction	System	Gefapixant 15 mg	Gefapixant 45 mg
Pneumonia	Infections and infestations	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—
Bronchitis	Infections and infestations	—	—
Pneumonia bacterial	Infections and infestations	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—
Hypophagia	Metabolism and nutrition disorders	—	—
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Ovarian germ cell teratoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Embolic cerebral infarction	Nervous system disorders	—	—

Other adverse events (18 terms — click to expand)

Reaction	System	Gefapixant 15 mg	Gefapixant 45 mg
Dysgeusia	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Hypogeusia	Nervous system disorders	—	—
Bronchitis	Infections and infestations	—	—
Taste disorder	Nervous system disorders	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
Pharyngitis	Infections and infestations	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Paraesthesia oral	Gastrointestinal disorders	—	—
Accidental overdose	Injury, poisoning and procedural complications	—	—
Ageusia	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—

Most-reported serious reactions: Pneumonia, Asthma, Large intestine polyp, Hepatic function abnormal, Bronchitis, Pneumonia bacterial, Radius fracture, Hypophagia.

Data from ClinicalTrials.gov NCT03696108 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the safety of two doses of gefapixant (MK-7264) in Japanese adult participants with refractory or unexplained chronic cough.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis.
   Kum E, Patel M, Diab N, Wahab M, et al · · 2023 · cited 27× · PMID 37694849 · DOI 10.1001/jama.2023.18035
2. A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough.
   Niimi A, Sagara H, Kikuchi M, Arano I, et al · · 2022 · cited 12× · PMID 35752582 · DOI 10.1016/j.alit.2022.05.006
3. Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials.
   Abu-Zaid A, Aljaili AK, Althaqib A, Adem F, et al · · 2021 · cited 12× · PMID 34012479 · DOI 10.4103/atm.atm_417_20